MOTIVIATION - One of MRI's inherent biophysical contrast parameters is proton self-diffusion, which can be measured by diffusion-weighted imaging (DWI). A variant, Diffusion Tensor Imaging (DTI), is an MRI method for noninvasive quantitative mapping of anisotropic water diffusion, thereby allowing the non-invasive investigation of white matter (WM) microstructure which might aid in the diagnosis and understanding the pathophysiology of white matter abnormalities and delayed maturation. DTI has been also used extensively for non-invasive tracing of WM pathways in tumor patients and in patients harboring non-focal disease. Unfortunately, DTI still suffers not only from physiologic motion but also from profound technical difficulties that increase with higher magnetic fields;higher magnetic fields on the other hand would offer substantially more signal-to-noise ratio (SNR). One of the major benefactors from motion-compensated DTI at high field would be children because of their smaller head sizes and the higher likelihood of motion. AIMS - The overarching goal of this 2-year research effort is to improve diffusion-weighted multi-shot spiral imaging to create significant improvements in 2D and 3D diffusion tensor imaging. Specifically, the project focuses on improvements for spiral acquisition methods and corresponding reconstruction techniques that reduce distortions, improve immunity to motion, diminish RF deposition, and provide better spatial resolution. Special emphasis is also given on improving image quality of this sequence for pediatric imaging. The specific aims are: (Specific Aim #1) to develop and optimize acquisition and reconstruction methods for real-time spiral diffusion-weighted MRI for 2D and 3D acquisitions;(Specific Aim #2) to define optimal DTI scan parameters for 2D and 3D for adults and children at 3T and 7T for different clinical applications and variants of motion. METHODS - Navigator, (prospective and retrospective) motion and off-resonance correction schemes in concert with augmented parallel imaging reconstruction algorithms will be developed and optimized both in simulations and phantom studies. Healthy children (n=62) and adults (n=30) will be enrolled for extensive testing. Optimal DTI scan parameters for a battery of different clinical questions and variants of motion will be determined by experienced neuroimagers and neuroradiologists. The raw k-space data and high-resolution diffusion tensor data will be added to a registry and can be made available to the public to improve image reconstruction algorithms (e.g. off-resonance correction, parallel imaging, diffusion phase navigation, gridding reconstruction), tensor processing (e.g. studying partial volume effects, crossing fibers, complex tract tracing algorithms) and to provide a normative database for adults and children that can be used in future trials. SIGNIFICANCE -We believe that upon successful completion of this project significant improvements in DTI can be achieved that will improve morphometric assessment and tract tracing in patients harboring various pathologic conditions. Abnormalities in WM and tract projections could provide crucial insights in the pathophysiology of several diseases that attack white matter, and further the understanding of specific neurodevelopmental trajectories of children with and without WM disorders.